Vol 15, No 1 (2017)

Progress in using the drugs based on hydrobionts in treatment of respiratory viral infections and their complications
Katelnikova A.E., Makarov V.G., Vorobieva V.V., Pozharitskaya O.N., Shikov A.N., Shabanov P.D.

The data of possibilities to use biologically active compounds, peptides and polysaccharides in particular, from sea urchins as potent sources of drugs are represented in the article. Their ability to act on the main chains of pathogenesis of the respiratory viral infections has been shown. So peptides and polysaccharides possess anti-inflammatory action due to inhibition of cyclooxygenase and inhibition of MAP kinase p38 phosphorylation, as well as antioxidant, immune correcting, antiviral and antibacterial effects. The progress in searching new drugs based on glycopeptides from sea urchins for treatment of respiratory tract infections and their complications are discussed.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):4-13
Place of piracetam in the modern practice of medicine
Vostrikov V.V.

The review considers the stages of experimental and clinical study of piracetam in the framework of evidence-based medicine, its wide practical application in various fields of clinical medicine. The main attention pays to the mechanisms of action of the drug, its properties and physiological effects. The specific dose-dependent relation is revealed for the clinical effects of piracetam: the efficiency grows higher dependent on high doses and prolongation of courses.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):14-25
Combined preconditioning with tetra-(1-vinylimidazole) cobalt dichloride
Levchenkova O.S., Novikov V.E., Kulagin K.N.

The aim of this study was to investigate the vinylimidazole derivative as pharmacological preconditioning in experimental acute hypoxia and cerebral ischemia. All experiments were conducted with mice and rats. Acute hypoxia with hypercapnia was modeled by placing the mice in a glass with a glass lid shtanglazy 250 ml. Acute hypobaric hypoxia was performed putting animals under a glass cope, where from the Kamovsky pump pumped up the air which is equal to the altitude of 5000 meters (moderate hypoxia) and 11 000 meters (severe hypoxia). Cerebral ischemia in rats was modeled by one-stage bilateral common carotid artery occlusion. Separate pharmacological and hypoxic preconditioning and combined preconditioning by alternately use of pharmacological and hypoxic factors were investigated. It was revealed that combined preconditioning (tetra-(1-vinylimidazole) cobalt dichloride 30 mg/kg + moderate hypobaric hypoxia) enhance the resistance of the animal organism to acute hypoxia in the early period (in 1 hr) and delayed period (in 48 hr) more effective than the separate preconditioning by moderate hypoxia or with the help of tetra-(1-vinylimidazole) cobalt dichloride. The combined preconditioning increase the survival of rats in the early periods and in the delayed periods of cerebral ischemia performance, but doesn’t reduce the severity of neurological deficit in the surviving animals registered with the Stroke Index McGraw scale.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):26-32
Pharmacological analysis of changes in the contentof diene conjugation, methyl esters of fatty acids of liver lipid fractions by cholinotropic agents during the overcooling of rats
Tikhanov V.I., Shabanov P.D.

The analysis of changes in the content of diene conjugation, fatty acid methyl esters (FAME) C20 of total lipids, fractions of free fatty acids (FFA) in the liver of animals exposed to overcooling for 3 hours and for 5 days after administration of cholinergic agents has been made. The obtained results indicate changing in the content of methyl esters of fatty acids and diene conjugation of FFA fractions after administration of pharmacological agents as neostigmine, pilocarpine, and atropine to animals on the background of cooling. Changes in the content of diene conjugation coincide with changes in the content of fatty acids (FA) C20 : 4 Δ-5,8,11,14 eicosatetraenoic acids (FA Arakhia) when pilocarpine or atropine was used. The presence of reciprocity was revealed. Basing the reciprocity factor, it was suggested that there was a possible effect of muscarine-sensitive structures of the plasmic membrane hepatocytes on the link between the content of FAME C20 Arakhia, phospholipase A2 activity and the change in the content of diene conjugation in fraction of liver FFA. A possible effect of cholinotropic agents on phospholipase A2 activity in the period of animal cooling was suggested.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):33-40
Study of reinforcing properties of new antagonists of glutamate receptors
Potapkin A.M., Lebedev A.A., Gmiro V.E., Litasova E.V., Brusina M.A., Piotrovskii L.B., Shabanov P.D.

Reinforcing properties of antagonists of NMDA receptors IEM-1921, IEM-1791, IEM-2181 and the antagonist of AMPA receptors IEM 1460 were investigated. Substances have been synthesized in S.V. Anichkov Dept. of Neuropharmacology Institute of Experimental Medicine. Electrodes were implanted into the lateral hypothalamus for brain stimulation reward. Rats were trained to press a pedal in Skinner box for receiving electric stimulation of the brain. IEM-1921 in doses of 1, 3 and 10 mg/kg enhanced number of pedal pressing and reduced self-stimulation thresholds more than phencyclidine (in doses 1, 3, 10 mg/kg) and MK-801 (in dose 1 and 3 mg/kg). IEM-1460 in doses of 1, 3 and 5 mg/kg reduced the frequency of hypothalamic self-stimulation and enhanced it thresholds. Also we investigated the conditional reinforcing properties of antagonists of glutamate receptors in conditional place preference test (CPP). The antagonist of NMDA receptors IEM 1921 did not cause CPP. The antagonist of AMPA receptors IEM 1460 caused CPP in dose of 3 mg/kg. IEM 1791 didn’t cause CPP. At the same time IEM 2181, the IEM 1791 water-soluble salt, caused CPP. Thus, the antagonist of NMDA of receptors of IEM-1921 increases the reinforcing properties of self-stimulation in rats more than phencyclidine and MK-801.This substance can be used as means analyzer for studying of the reinforcing properties of drugs. Antagonist of NMDA receptors IEM 2181cause CPP and has the conditional reinforcing properties. It is interesting that the antagonists of AMPA receptors IEM 1460 partially cause CPP, but reduced the reinforcing properties of self-stimulation.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):41-47
Individual peculiarities in pharmacokinetics of antiblastomic drugs in healthy volunteers
Oseshnyk R.A., Ushal I.E., Svetkina E.V., Kolobova E.A., Strukov Y.V., Rodionov G.G., Shabanov P.D.

The data of inter-individual variations in pharmacokinetics of antiblastomic drugs from the group of tyrosine proteinkinase inhibitors (imatinib, gefitinib and nilotinib) and antiblastomic immune modulator lenalidomide in healthy volunteers by meams of HPLC-MS/MS were represented in the article. The concentrations of the drugs studied were measured in the volunteer blood serum. The indeces Cmax (maximal concentration and time reaching), Tmax (time covering maximal concentration measure), AUC0-t (squire under pharmaceutical curve) were processed by trapetias method, Cmax/AUC0-t as well as Kel (elimination constant) and T1/2 (period of semielimination) according to individual signs. The significant individual variability revealed for imatinib, gefitinib and nilotinib in healthy volunteers indicates on necessity of therapeutic drug monitoring in patients treated with them to aim optimal dosing.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):48-52
The influence of phlomoides tuberosa extract on structure of spleen in immunosupressive mice
Tsyrenova D.Z., Gulyaev S.M., Khobrakova V.B.

Background. The immune system is extremely sensitive to adverse external and internal factors. In this context, a correction of immunosuppressive states of immune organs by means of complex and safe means, such as the extraction of medicinal plants is required. In this regard, plants containing phenylpropanoids are of interest. It was shown that the extract from Phlomoides tuberosa L. Moench showed immunostimulatory activity due to the content phenylpropanoids.

Purpose. The present study was aimed at the estimation of the effect of P. tuberosa extract оn the spleen structure using experimental azathioprine immunosupression model.

Materials and methods. The experiments were carried out on CBA male mice, 20-22 g of weight. Immune deficiency was modeled by the intragastrical introduction of azathioprine in the dose 50 mg/kg once a day for 5 days. The experimantal group of animals received the tested remedy once a day intragastrically in dose 1 mg/kg for 14 days against the background of azathioprine immunosupression. The intact group received the purified water according to the analogous scheme. Data were obtained using histological, morphometric and statistical analysis.

Results. The results have shown that azathioprine caused disruptive changes in the structure of the lymphoid tissue of the spleen: area of white pulp and the thickness of the periarterial lymphoid sheath (PALS) were equally less – in 1.7 times, the diameters of the lymphoid nodules and germinative centers were lower, respectively in 2.6 and 1.7 times, compared with a negative control. The course administration of the test remedy to animals was significantly reduced suppressive effect of cytostatic azathioprine: area of white pulp and the thickness PALS spleens of mice treated with the extract were 1.5 and 1.4 times the diameters of lymphoid nodules and germinative centers was 2.1 times and 1.2 times more positive control.

Conclusion. Thus, the data obtained allow to conclude that the dry extract P. tuberosa has the marked immune modulating activity that substantiates the expediency of its further study in order to create new effective immune modulators.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):53-57
The experience of Avicenna and possibility to improve the diabetes treatment
Sharofova M.U.

This article provides an analysis of research on the impact of modern antidiabetic drugs on the patients and possible ways to improve the treatment of diabetes, based on the experience of Avicenna’s medicine. More and more doctors today practice complementary medicine, combining traditional techniques with non-traditional treatments, including herbal medicine. Studying of various side effects of hypoglycemic drugs showed that most of synthetic means cause numerous complications. Modern medicine is faced with the need to develop new approaches to diabetes treatment and medicines that help to achieve stable metabolic conditions and ensure the safety of medicines. A huge contribution to the study of diabetes has made Abu Ali ibn Sina, who cured the disease, based on the definition of “mizadzh” (nature) of human and drugs prescribed for its correction. There are many etiological factors contributing to insulin resistance and pre-diabetes and they often are interrelated. Based on the Avicenna’s theory of diabetogenezis, we subdivided prediabetes on prepankreatic and pancreatic stages. The onset of prediabetes Avicenna linked with impaired renal, liver and internal environment’s function of the body, which are based on acidosis, eventually contributing to the emergence of pre-diabetes and insulin resistance. Ibn Sina believed that the increased consumption of acidic foods causes a change of the “mizadzh” of the human body in a “cold” (sour, atsidic) diabetogenic side. Modern science has proved that the basis for the development of diabetes is a pH shift toward acidosis. Our studies have shown that the basis of Avicenna’s antidiabetic means comprise alkalizing agents of natural origin. On this basis, herbal medicine is an effective supplement to the officially accepted treatment methods based on the principles of evidence.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):58-67
Transport of heat through the skin
Luchakov Y.I., Shabanov P.D.

The transport of heat through the skin of the human body has been investigated in the paper. The analysis of cytoarchiterture of this region was done, a model of vascular stream of the skin was built where the transient microregion typical for its different tissues was separated. A mathematical model taking part both convective and conductive heat transport was reproduced for this microregion. There was no heat transfer through the blood but only conductive heat transport was shown to be in the superficial skin tissue strates having blood current. In the norm, there was convective heat transport preferably in the deeper skin strates of the hypoderm where arterials and veins of more than 100 and 300 um in diameter were lying. The organism was revealed to able to increase or decrease the skin region where there was only convective or conductive heat transport by means of changing the blood stream. Therefore, the organism is able to change the size of peripheral tissue where there is only convective or only conductive heat transfer according to physiological necessity.

Reviews on Clinical Pharmacology and Drug Therapy. 2017;15(1):68-71

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